Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MK-0822
odanacatib · 12 trials · 4 indications
Lumbar spine BMD was assessed by dual energy X-ray absorptiometry (DXA) at Baseline and at Month 24.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
aBMD (g/cm\^2) was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and mean BMD measurements from at least 3 evaluable lumbar spine vertebrae (L1-L4) were used. If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from the analysis and the lumbar spine BMD was recalculated based on the three remaining vertebrae. aBMD data was centrally evaluated and all areal BMD measurements included a longitudinal BMD correction factor as determined by the quality control center. aBMD at the lumbar spine was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal Analysis of Covariates (ANCOVA) model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as primary and secondary outcome measures, respectively.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's products, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The percentage of participants that experienced at least one AE was reported for each treatment arm.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's products, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The percentage of participants that discontinued study treatment (different from discontinuation of the study) due to an AE was reported for each treatment arm.
BMD at the femoral neck was assessed by dual-energy X-ray absorptiometry (DXA) at baseline and Month 24.
An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.
An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.
BMD (g/cm2) data was measured by dual-energy X-ray absorptiometry (DXA) at lumbar spine vertebrae 1 through 4 (L1-L4) from anterior view at the Observation visit (up to 5 weeks before Treatment Period), Week 0 (start of Treatment Period) and Week 52 (end of Treatment Period) or at discontinuation. Baseline was defined as the average of the 2 values collected at the Observation visit and Week 0 visit. Percent change from baseline in BMD = (\[BMD at Week 52 visit\] - \[baseline BMD\] ÷ baseline BMD) × 100. Measurements were performed using the Hologic Quantitative Digital Radiography (QDR) Series densitometer, and by same machine and under same scan mode throughout the study period. BMD data was centrally judged.
An AE was defined as any unfavorable and unintended change in the structure (sign), function (symptoms), or chemistry of the body (laboratory data) temporally associated with the use of the SPONSOR's products (including placebo), whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm.
An AE was defined as any unfavorable and unintended change in the structure (sign), function (symptoms), or chemistry of the body (laboratory data) temporally associated with the use of the SPONSOR's products (including placebo), whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The number of participants that discontinued study drug due to an AE was reported for each treatment arm. Participants may have discontinued study drug but continued on the trial.
Percentage change in lumbar spine BMD (relative to baseline) at 12 Months.
Percentage change in lumbar spine BMD (relative to baseline) at 24 Months.
Percentage change in lumbar spine BMD (relative to baseline) at 36 months
Percentage change from baseline in lumbar spine BMD at 60 months.
Percentage change from baseline in lumbar spine BMD at 120 Months.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
For healthy and moderate hepatic insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of AUC0-∞ (Total AUC). AUC0-∞ is a measure of total drug exposure.
uNTx/Cr is a biomarker of bone resorption. Urine samples were obtained predose on Day 1 (Baseline) and at various timepoints up to 336 hr postdose on Day 22 (Week 4). Fold change from baseline in time weighted average (TWA) of uNTx/Cr on log scale was analyzed via a linear mixed effect model. All analyses were carried out on the log-fold scale and final results were reported on the original percent scale in WAI after back transformation. The conversion used was weighted average inhibition (WAI) = (1-exp \[mean\])\*100, where the mean was the least squares (LS) mean of log-transformed ratio (TWA/baseline) from the above model.
| Arm | Type | Description |
|---|---|---|
| Odanacatib 50 mg once weekly | EXPERIMENTAL | Participants will receive one Odanacatib 50 mg tablet once weekly. In addition, they will receive a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources is approximately 1200 mg. |
| Placebo once weekly | PLACEBO_COMPARATOR | Participants will receive one Placebo tablet once weekly. In addition, they will receive a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources is approximately 1200 mg. |
| Odanacatib 50 mg | EXPERIMENTAL | Participants receive 50 mg odanacatib and open-label 5600 IU vitamin D3 tablets once weekly for 24 months. Participants also receive 500 mg of open-label daily calcium supplement as needed to ensure a total daily calcium intake of 1200 mg. |
| Placebo | PLACEBO_COMPARATOR | Participants receive matching placebo to odanacatib and open-label 5600 IU vitamin D3 once weekly for 24 months. Participants also receive 500 mg of open-label daily calcium supplement as needed to ensure a total daily calcium intake of 1200 mg. |
| Odanacatib 10 mg | EXPERIMENTAL | After an observation period of \~5 weeks, participants receive 10 mg odanacatib once weekly for 52 weeks. Participants also receive weekly supplementation with open-label 5600 IU vitamin D3 and 500 mg of open-label daily calcium supplement (if calcium \<1000 mg per day from dietary and other sources) throughout the observation and treatment periods. |
| Odanacatib 25 mg | EXPERIMENTAL | After an observation period of \~5 weeks, participants receive 25 mg odanacatib once weekly for 52 weeks. Participants also receive weekly supplementation with open-label 5600 IU vitamin D3 and 500 mg of open-label daily calcium supplement (if calcium \<1000 mg per day from dietary and other sources) throughout the observation and treatment periods. |
| Odanacatib 3 mg | EXPERIMENTAL | - |
| Moderate Hepatic Insufficiency Group | EXPERIMENTAL | Single-dose administration of odanacatib 50 mg to participants with moderate hepatic insufficiency. |
| Healthy Matched Control Group | EXPERIMENTAL | Single-dose administration of odanacatib 50 mg to healthy matched control participants. |
| Severe Renal Insufficiency Group | EXPERIMENTAL | Single-dose administration of odanacatib 50 mg to participants with severe renal insufficiency. |
| Panel A - Odanacatib | EXPERIMENTAL | Panel A - Healthy male subjects receiving Odanacatib |
| Panel A - Placebo | PLACEBO_COMPARATOR | Panel A - Healthy male subjects receiving placebo |
| Panel B - Odanacatib | EXPERIMENTAL | Panel B - Healthy female subjects receiving Odanacatib |
| Panel B - Placebo | PLACEBO_COMPARATOR | Panel B - Healthy female subjects receiving placebo |
| 1 | EXPERIMENTAL | MK0822 |
| 2 | PLACEBO_COMPARATOR | Placebo to MK0822 |
| A | EXPERIMENTAL | Panel A |
| B | EXPERIMENTAL | Panel B |
| C | EXPERIMENTAL | Panel C |
| D | EXPERIMENTAL | Panel D |
| Name | Type | Description |
|---|---|---|
| Odanacatib | DRUG | One 50 mg tablet once weekly |
| Placebo for Odanacatib | DRUG | One 50 mg tablet once weekly |
| Vitamin D3 | DIETARY_SUPPLEMENT | 5600 IU of open-label Vitamin D3 once weekly |
| Calcium carbonate | DIETARY_SUPPLEMENT | Sufficient amount of open-label calcium carbonate so that daily calcium intake from both dietary and supplementary sources in approximately 1200 mg |
| Placebo | DRUG | Matching placebo tablets to odanacatib taken orally once weekly for 24 months. |
| Calcium supplement | DRUG | Calcium supplement 500 mg tablet taken orally once daily (up to \~1200 mg total) for 24 months. |
| Calcium | DIETARY_SUPPLEMENT | Participants will receive calcium carbonate supplements as needed to ensure a daily calcium intake of 1200 mg. |
| MK-0822 | DRUG | A single oral dose (50 mg tablet) of MK 0822 will be administered on Day 1 after an overnight fast. |
| Comparator: Placebo | DRUG | Oral Placebo tablet administered once weekly for 4 consecutive weeks |
| Comparator: placebo to MK0822 | DRUG | Panel A: placebo to MK0822 tablets 25 mg once weekly for 3 weeks. Panel B: placebo to MK0822 tablets 50 mg once weekly for 3 weeks. Panel C: placebo to MK0822 tablets 100 mg once weekly for 3 weeks. Panel D: placebo to MK0822 tablets 5 mg once weekly for 3 weeks. Panel E: placebo to MK0822 tablets 100 mg once weekly for 6 weeks. |
| Comparator: odanacatib (Panel B) | DRUG | Panel B: Odanacatib tablets will be administered to male subjects in rising single doses of 5, 25 (fasting), 100, 25 (fed), or 600 mg over 5 treatment periods. Each subject will receive placebo to odanacatib in one or two of the 5 treatment periods. There will be at least 7 days between each treatment period. |
| Comparator: odanacatib (Panel C) | DRUG | Panel C: Odanacatib tablets will be administered to female subjects in rising single doses of 50 or 100 mg over 2 treatment periods. Half of the subjects will receive placebo to odanacatib in one of the 2 treatment periods. There will be at least 7 days between each treatment period. |
| Comparator: odanacatib (Panel D) | DRUG | Panel D: Odanacatib tablets or placebo to odancatib will be administered to male subjects in rising single doses of 100, 200, or 300 mg following a high-fat breakfast over 3 treatment periods. Three of twelve subjects will receive placebo to odanacatib in all 3 treatment periods. There will be at least 10 days between each treatment period. |
Inclusion Criteria: * Is a male between 40 and 95 years of age * Has osteoporosis * Has anatomy suitable for dual energy x-ray absorptiometry (DXA) scan of the lumbar spine and and hip * Is ambulatory Exclusion Criteria: * Is currently on oral bisphosphonates or other treatment for osteoporosis *...
Odanacatib was developed for the treatment of osteoporosis, including postmenopausal osteoporosis. It was studied in men with osteoporosis as well as in postmenopausal women, including women previously treated with a bisphosphonate. It is an investigational therapy and is not approved for use.
Odanacatib targets cathepsin K (CTSK) and acts as an inhibitor of this enzyme. Cathepsin K is involved in bone resorption, and inhibiting it is the mechanism by which odanacatib was designed to reduce bone breakdown in osteoporosis.
Odanacatib is developed by Merck & Company, Inc., which trades under the ticker MRK. The compound is also referenced by the code MK-0822 in its clinical program.
Odanacatib reached Phase 3 clinical development for osteoporosis. It is an investigational small molecule and is not approved. Nine trials are recorded for the program, all of which are completed, with no active trials currently listed.
Odanacatib has been studied across nine completed trials. These include the Phase 3 NCT01120600 study in men with osteoporosis, the Phase 2 NCT00885170 study in postmenopausal women previously treated with a bisphosphonate, and the Phase 1 trials NCT01068262 and NCT00863590.
The odanacatib clinical program enrolled a total of 1,369 participants across its nine completed trials. The studies were randomized, double-blind, and controlled, and they covered both men with osteoporosis and postmenopausal women.